ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.974G>A (p.Gly325Asp) (rs398123228)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000157881 SCV000110146 pathogenic not provided 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000157881 SCV000207812 pathogenic not provided 2012-11-28 criteria provided, single submitter clinical testing The Gly325Asp mutation in the GLA gene has been reported in association with Fabry disease (Schafer E et al., 2005; Wu X et al., 2011). Mutations affecting nearby residues (Asp322Gly, Gln327Glu, Gln327Lys) have also been reported in association with Fabry disease, further supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Gly325Asp was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations.In summary, Gly325Asp in the GLA gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).
Invitae RCV000078306 SCV000622197 pathogenic Fabry disease 2017-05-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 325 of the GLA protein (p.Gly325Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (rs398123228, ExAC no frequency). This variant has been reported in individuals affected with Fabry disease (PMID: 15713906, 15776423, Invitae). ClinVar contains an entry for this variant (Variation ID: 92574) Experimental studies have shown that this missense greatly reduces GLA enzymatic activity (PMID: 15713906, 19387866 , 21598360). For these reasons, this variant has been classified as Pathogenic.

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